{"doi":"10.1084/jem.20230930","title":"Plasticity of intragraft alloreactive T cell clones in human gut correlates with transplant outcomes","abstract":"The site of transition between tissue-resident memory (TRM) and circulating phenotypes of T cells is unknown. We integrated clonotype, alloreactivity, and gene expression profiles of graft-repopulating recipient T cells in the intestinal mucosa at the single-cell level after human intestinal transplantation. Host-versus-graft (HvG)-reactive T cells were mainly distributed to TRM, effector T (Teff)/TRM, and T follicular helper compartments. RNA velocity analysis demonstrated a trajectory from TRM to Teff/TRM clusters in association with rejection. By integrating pre- and post-transplantation (Tx) mixed lymphocyte reaction-determined alloreactive repertoires, we observed that pre-existing HvG-reactive T cells that demonstrated tolerance in the circulation were dominated by TRM profiles in quiescent allografts. Putative de novo HvG-reactive clones showed a transcriptional profile skewed to cytotoxic effectors in rejecting grafts. Inferred protein regulon network analysis revealed upstream regulators that accounted for the effector and tolerant T cell states. We demonstrate Teff/TRM interchangeability for individual T cell clones with known (allo)recognition in the human gut, providing novel insight into TRM biology.","journal":"The Journal of Experimental Medicine","year":2023,"id":337842,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":18,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9554,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1069806,"name":"Zicheng Wang","orcid":"0000-0001-6128-296X","position":1,"is_corresponding":false},{"id":239748,"name":"Mercedes Martínez","orcid":"0000-0001-6128-0155","position":2,"is_corresponding":false},{"id":266898,"name":"Aleksandar Obradović","orcid":"0000-0002-8009-0186","position":3,"is_corresponding":false},{"id":1069807,"name":"Wenyu Jiao","orcid":"0000-0002-0189-4312","position":4,"is_corresponding":false},{"id":677330,"name":"Kristjana Frangaj","orcid":"0009-0008-3723-574X","position":5,"is_corresponding":false},{"id":1069808,"name":"Rebecca Jones","orcid":"0000-0002-0970-1968","position":6,"is_corresponding":false},{"id":105627,"name":"Xinzheng V. 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